Vaccines play a role in the prevention and treatment of diseases, including cancer and infections. For some conditions, e.g., malaria, few effective vaccines are available. Vaccine studies using irradiated sporozoites have demonstrated the theoretical feasibility of an effective vaccine to protect against the pre-erythrocytic stages of malaria infection. Subsequent studies have shown that the protection observed in murine model systems of malaria can involve both humoral and cell-mediated immunity, but can depend on the activity of T lymphocytes, presumably due to the need to destroy infected cells within the liver. Although interest persists in the use of irradiated sporozoites as a malaria vaccine, the feasibility of this approach remains to be established.
DNA vaccines can be used to treat a variety of conditions. DNA vaccines can target dendritic cells (DC). DCs play a role in regulating immune responses, including determining whether immunity or tolerance is generated and whether, if immunity is generated, Th1 or Th2 T cells or both are recruited to the response. The different outcomes of presentation of antigens by DC can be influenced by the progenitor cells that gave rise to a particular class of DC, by tissue localization of the DC involved in a given response, by differences in the activating stimulus, which can be reflected by what cytokines a DC produces and, of particular relevance for this proposal, by the state of maturation of the DC, as indicated by surface protein expression profile.
There is a need for the development of, and improvement of, vaccines, e.g., DNA vaccines, to treat conditions such as malaria, cancer, and Alzheimer's disease.